Visible light-induced apoptosis activatable nanoparticles of photosensitizer-DEVD-anticancer drug conjugate for targeted cancer therapy

Wooram Um, Jooho Park, Hokyung Ko, Seungho Lim, Hong Yeol Yoon, Man Kyu Shim, Sangmin Lee, Young Ji Ko, Min Ju Kim, Jae Hyung Park, Dong Kwon Lim, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The therapeutic efficacy of photodynamic therapy (PDT) in cancer treatment is attributed to the conversion of tumor oxygen into reactive singlet oxygen (1O2) using photosensitizers. However, poor tissue penetration and rapid oxygen depletion have limited the effectiveness of PDT. Therefore, we have developed visible light-induced apoptosis activatable nanoparticles of the photosensitizer (Ce6)-caspase 3 cleavable peptide (Asp-Glu-Val-Asp, DEVD)-anticancer drug monomethyl auristatin E (MMAE) conjugate, resulting in Ce6-DEVD-MMAE nanoparticles. The average size of self-assembled Ce6-DEVD-MMAE nanoparticles was 90.8 ± 18.9 nm. Compared with conventional PDT based on high-energy irradiation, the new therapy uses lower-energy irradiation to induce apoptosis of cancer cells, and activation of caspase 3 to successfully cleave the anticancer drug MMAE from the Ce6-DEVD-MMAE nanoparticles, resulting in strong cytotoxic effects in cancer cells. Notably, the one-time activation of MMAE in the Ce6-DEVD-MMAE nanoparticles further amplified the cytotoxic effect resulting in additional cell death in the absence of visible light irradiation. Furthermore, Ce6-DEVD-MMAE nanoparticles passively accumulated in the targeted tumor tissues via enhanced permeation and retention (EPR) effect in mice with squamous cell carcinoma (SCC7). The high levels of toxicity were retained after exposure to lower-energy irradiation. However, Ce6-DEVD-MMAE nanoparticles did not show any toxicity in the absence of exposure to visible light irradiation, in contrast to the toxicity of free MMAE (1–10 nM). Thus, the light-induced therapeutic strategy based on apoptotic activation of Ce6-DEVD-MMAE nanoparticles can be used to treat solid tumors inaccessible to conventional PDT.

Original languageEnglish
Article number119494
JournalBiomaterials
Volume224
DOIs
Publication statusPublished - 2019 Dec 1

Keywords

  • Apoptosis
  • Cytotoxic prodrug
  • Nanomedicine
  • Photodynamic therapy
  • Self-assembly
  • Targeted cancer therapy

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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